Figure 5.

Depletion of Id1 abrogates chemoresistant phenotype and tumorigenic properties of pancreatic cancer cells. (A) Depletion of Src and Id1 using siRNA induces PARP cleavage in L3.6pl^GemRes-acquired.resistant pancreatic cancer cells exposed to gemcitabine therapy. (B) Depletion of Id1 expression in innate chemoresistant PANC-1 cells induces PARP cleavage and resensitizes cells to the cytotoxic effects of gemcitabine. (C) Tumor growth monitored by luciferase activity (photons per second) over approximately 4 weeks demonstrates increased tumor burden in mice treated with nicotine, whereas Id1 depletion resulted in inhibition of tumor growth regardless of nicotine exposure. (D) Graph showing the corresponding tumor volume (mm³) from each animal group corresponding to in vivo luciferase imaging of mice at termination of experiment (inset) demonstrating the promoting effects of nicotine and the suppressive effects of Id1 silencing on primary tumor growth. (E) Nicotine-induced pSrc and Id1 expression levels in primary tumors in vivo while having no effect on Id1 expression in tumors originating from cells with stably transfected shRNA silencing of Id1. (F) Ex vivo quantification of luciferase activity (photons per second) from livers demonstrates significantly higher liver metastasis in mice treated with nicotine while demonstrating no liver metastasis in mice with tumors derived from Id1-depleted cells. (G) H&E staining of livers (N) with metastatic pancreatic tumor demonstrates increased expression of Id1 in metastatic deposits (M).